Jara, AlejandroUndurraga, Eduardo A.Zubizarreta, José R.González, CeciliaPizarro, AlejandraAcevedo, JohannaLeo, KatherinneParedes, FavioBralic, TomásVergara, VerónicaMosso, MarceloLeón, FranciscoParot, IgnacioLeighton, PaulinaSuárez, PamelaRíos, Juan CarlosGarcía-Escorza, HeribertoAraos, Rafael2023-07-102023-07-102022Jara, Alejandro and Undurraga, Eduardo A. and Zubizarreta, José R. and Gonzalez, Cecilia and Pizarro, Alejandra and Acevedo, Johanna and Leo, Katherinne and Paredes, Fabio and Bralic, Tomas and Vergara, Veronica and Mosso, Marcelo and Leon, Francisco and Parot, Ignacio and Leighton, Paulina and Suarez, Pamela and Rios, Juan Carlos and García-Escorza, Heriberto and Araos, Rafael, Effectiveness of Homologous and Heterologous Booster Shots for an Inactivated SARS-CoV-2 Vaccine: A Large-Scale Observational Study. http://dx.doi.org/10.2139/ssrn.4005130https://repositorio.udd.cl/handle/11447/7678Background: Vaccine protection against Covid-19 may be waning. Several countries have authorized or begun using a booster vaccine dose. Policymakers urgently need evidence of the effectiveness of additional vaccine doses against Covid-19 and its clinical spectrum for individuals with complete primary immunization schedules. Methods: We used a prospective national cohort of 11·2 million persons 16 years or older to assess the effectiveness of CoronaVac, AZD1222, or BNT162b2 vaccine boosters in individuals who completed their primary immunization schedule with CoronaVac compared to unvaccinated individuals. The study was conducted in Chile from February 2 through November 10, 2021. We used inverse probability-weighted survival regression models to estimate hazard ratios, accounting for time-varying vaccination status and adjusting for relevant demographic, socioeconomic, and clinical confounders. We estimated the change in the hazard associated with complete immunization (≥14 days after the booster). Findings: We found an adjusted vaccine effectiveness against symptomatic Covid-19 of 78·8% (95% confidence interval, CI, 76·8–80·6) for a three-dose schedule with CoronaVac, 96·5% (95% CI, 96·2–96·7) for BNT162b2 booster, and 93·2% (95% CI, 92·9–93·6) for the AZD1222 booster. The adjusted vaccine effectiveness against hospitalization, ICU admission, and Covid-19 related deaths was 86·3%, 92·2%, and 86·7% for a three-dose schedule with CoronaVac, 96·1%, 96·2%, and 96·8% for the BNT162b2 booster, and 97·7%, 98·9%, and 98·1% for the AZD1222 booster. Interpretation: Our results suggest that a homologous or heterologous booster shot for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against Covid-19, including severe disease and death. However, heterologous boosters showed higher vaccine effectiveness for all outcomes, providing additional support for using a mix and match approach. Funding Information: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The research protocol was approved by the Comité Ético Científico Clínica Alemana Universidad del Desarrollo. The study was considered exempt from informed consent, no human health risks were identified. Research analysts belong to the Chilean Ministry of Health; our use of data follows Chilean law 19·628 on personal data protection.enSARS-CoV-2Covid-19Vaccine effectivenessInactivated SARS-CoV-2 vaccineImmunization programBoostersArticlehttp://dx.doi.org/10.2139/ssrn.4005130